giant cell lesions in bone - Shilpa Gupta.pptx

GIANT CELL LESIONS OF BONE

1. Pre test- What is the diagnosis of the following cases? 1

2. Case 1 32 year old man 2

3. Case 2 18 year old man with 2 year history of mild knee pain 3

4. Case 3 A 65-year-old Caucasian male 4

5. Case 4 5 A 56 year old woman presented with history of left cheek swelling for last 5 years CT scan (Coronal) showing expansile and destructive lesion involving left maxilla

6. Intra operative picture showing extensive tumor being excised 6

7. Case 5 15 year old girl 7

8. GIANT CELLS IN THE LESIONS OF BONE Presentor - Dr Shilpa Gupta Moderator- Dr Mahesh Karigoudar 8

9. Headings- Giant cell introduction Introduction of giant cell lesions of bone Classification of lesions Individual lesion per se APPROACH TO THE GIANT CELL LESIONS Summary References 9

10. Giant cell (Osteoclasts) Introduction- Osteoclasts, as named by Kolliker are bone-resorbing cells that play a pivotal role in bone homeostasis and remodeling. Osteoclast precursors are derived from bone marrow as early mononuclear macrophages, which circulate in blood, and bind to the surface of bone. Osteoclast formation is driven mainly by two cytokines, Receptor Activator of Nuclear Factor Kappa β Ligand (RANKL) and macrophage - colony stimulating factor (M-CSF). In addition a wide variety of factors like systemic hormones and growth factors influence the formation and function of osteoclasts. 10

11. They usually contain 10 to 20 nuclei per cell and are found on bone surfaces; on the endosteal surfaces in shallow concavities called Howship lacunae and on the periosteal surface beneath the periosteum . 11

12. Giant Cell s in the lesions of Bone 12

13. Introduction Giant cell rich lesions encompass a relatively large group of biologically and morphologically diverse bone tumours. They are all related to one another by the presence of numerous multinucleated osteoclast-like giant cells. The morphologic characteristics, combined with the striking consistency in age and site distribution make the diagnosis fairly straight forward in most instances. 13

14. However, they differ from each other by virtue of their clinical and radiographic characteristics and in their morphology. In select cases, immunohistochemistry may be necessary to make an accurate diagnosis. The importance of correctly identifying these tumours rests on the differences in their treatment and prognosis. 14

15. Classification A. Reactive : Brown tumor Hemophiliac Pseudotumor Intraosseous haemorrhage B. Benign : GC Granuloma Non ossifying Fibroma GC Tumor Aneurysmal Bone Cyst Chondroblastoma Chondromyxoid Fibroma Langerhans Cell Histiocytosis Pigmented Villonodular Synovitis 15

16. C. Malignant Osteosarcoma Clear cell chondrosarcoma Metastatic Carcinoma 16

17. Brown tumours , are unifocal or multifocal bone lesions L esion de r ives i ts na m e f rom the color of the tis s ue s p e ci m en( r e d -bro w n) , d ue to abundant hemosiderin deposition within the tumor . affects especially females, ratio 3:1. Mainly in 30 to 60 years of age. It can affect the base of the skull, orbits, paranasal sinuses, spinal column ,as well femur, tibia, humerus , clavicles and scapula. Brown Tumor of hyperparathyroidism 17

18. Radiologic features C la s sic sign is subperiosteal erosion along the radial m argin of the middle phalenges. They appear as uni l o c u l a r or multilocular with variably defined margin and may produce cortical expansion. • Hand bone—earliest change is subtle erosion of bone from sub- periosteal surface of phalanges of hand. 18

19. Pathological calcification— Punctuate and nodular calcifications occasionally occur in kidneys and joints. Skull bones—entire calvarium has granular appearance caused by loss of central trabeculae and thinning of cortical tables. Pepper pot skull—evidence in the skull vault of osteopenia producing a fine overall stippled pattern to the bone, hence it is called as pepper-pot skull . 19

20. Microscopy : Similar to central giant cell granuloma. P roliferation of vascular granulation tissue which serves as a back ground for numerous osteoclastic MGC. Hemosiderin deposition . Vasularity and hemosiderin content imparts the color. 20

21. Central Giant Cell Granuloma Etiology unknow n The incidence of CGCG 0.0001%. Gender predilection - female–male ratio of approximately 2:1 The CGCG of the jaw accounts for approximately 7% of all tumors of the jaw. It may occur at any age but is more commonly seen in the first three decades of life. 21

22. T he earliest sign of the lesion may be expansion of bone with premature loosening and shedding of deciduous teeth. Usually painless Based on C/F & R/F : it is classified as Non-aggressive—it exhibits slow growing benign behavior. Aggressive—it shows typical features of rapidly growing, destructive lesion. 22

23. -Aggressive lesions may exhibit pain,rapid growth,cortical perforation and root resorptio -Non aggressive exhibit no symptoms,slow growth,no perforation,no resorption 23

24. Radiographic features Radiographically, central giant cell granulomas present as either unilocular or multilocular radiolucencies. Multilocular lesions are usually larger than unilocular lesions but either may show radiographic evidence of expansion. The radiolucency may be ill defined or may have corticated borders. "Fuzzy" densities and "wispy" opacifications may be seen within the radiolucent areas and are thought to represent mineralized trabeculae. 24

25. Microscopy O val or spindle-shaped mesenchymal cells V arying number of multinucleated giant cells F ibrous stroma I n a perivascular or adjacent position to areas of hemorrhage . Round macrophages, deposition of hemosiderin, extravasated erythrocytes, foci of osteoid material (bone trabeculae), dystrophic calcification and predominantly mononuclear inflammatory infiltrate, particularly surrounding the periphery of the lesion found . 25

26. Metaphyseal fibrous defect It is a non-neoplastic process, possibly related to defect in ossification. Occurs under the age of 10 years. Classically involves metaphysis Fibrous cortical defect- When confined to cortex. Lesion enlarges and extends into the adjacent medullary cavity- Non-ossifying fibroma. Sites- Distal femur, proximal and distal tibia. Associated syndromes- Neurofibromatosis and Jaffe Campanacci syndrome. Asymptomatic and are discovered incidentally. 26

27. Metaphyseal fibrous defect of lower end of tibia. Sharp delineation and sclerotic margins. Large metaphyseal fibrous defect expanding lower tibial metaphysis. 27

28. Grossly- Lesion is tan brown on color with areas of yellow discoloration. Cystic changes may be present. Haemorrhage and necrosis due to pathological fracture. Mic r os c opy- Spindle fibroblasts arranged in storiform pattern. Spindle cell have cytologically bland nuclei, that have pointed ends and eosinophillic cytoplasm. Osteoclast type giant cells. Few mitosis. Haemosiderin deposits and foamy macrophages. 28

29. Metaphyseal fibrous defect. The predominant element is a spindle cell of fibroblastic appearance. There are also irregularly scattered osteoclasts. 29

30. Myositis ossificans History of trauma Common locations- flexor muscles of the upper arm, quadriceps femoris, adductor muscle of the thigh, gluteal muscles and soft tissues of the hand. X ray- Periosteal reaction and faint soft tissue calcification within 3-6 weeks of injury. Gradually replaced by mature heterotopic bone by 10-12 weeks. 30

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32. Gross- Shell of bony tissue with more or less soft red brown central area. Usually 2-5 cm in diameter and adherent to the surrounding muscle. 32

33. Myositis ossificans. Peripheral portion showing a shell of well-formed bone. 33 Microscopy-

34. Myositis ossificans. Midportion showing osteoid formation by plump osteoblasts. 34

35. Langerhan’s cell histiocytosis It is defined as an intraosseous mass of proliferating Langerhans cells. They are dendritic cells and normally populate the skin, mucosal surfaces, lymph nodes, where they function as antigen presenting cells. Single or multpile lesions restricted to the skeleton have been termed as eosinophilic granuloma. Common during first three decades of life. Males are affected more than females. The disease usually manifests in skeleton, skin, lung and lymph nodes. In skeleton most common- skull, jaw, vertebral bodies, ribs, pelvis and long bones. 35

36. X ray- Well defined, lytic lesions. Cortical involvement may elicit periosteal reaction. 36

37. Gross- Non-specific, gritty, tan appearance. Microscopy- The proliferating Langerhan’s cells are ovoid/round, histiocyte like cells, 10-15 um in diameter that are arranged in aggregates, sheets or within loose fibrous stroma. Cells have eosinophilic cytoplasm and contain central, ovoid coffee bean shaped nuclei. 37

38. Coffee bean appearance of the nuclei. Most of the Langerhan’s cells are mononuclear but some cells contain multiple nuclei, which tend to be centrally located. Accompanying infiltrate of eosinophils which may be so dense that it obscures underlying Langerhan’s cells . Lymphocytes, plasma cells, macrophages, neutrophils, osteoclast-type giant cells can also be seen. 38

39. Langerhan’s cell histiocytosis of skull. A sharp, well circumscribed, dark brown lesion is seen. 39

40. Langerhans ’ cell histiocytosis. Polymorphic appearance resulting from an admixture of Langerhans’ cells, nonspecific histiocytes, lymphocytes, and eosinophils. There is a mild atypia in the Langerhans’ cells that can simulate a malignant process. 40

41. Langerhan’s cell histiocytosis 41

42. This cell from Langerhans ’ cell histiocytosis of bone contains several Birbeck's granules (arrows) 42

43. Rosai-Dorfman’s disease Sinus histiocytosis with massive lymphadenopathy. Involves skin, upper respiratory tract, lymph node and bone. Second and third decade of life. In bones- Skull, facial bones, ribs and vertebrae. 43

44. X ray- Well circumscribed radiolucency confined within the bone without soft tissue or periosteal reactions. Microscopy- Heterogenous population of histiocytes, lymphocytes, plasma cells and neutrophils which can form microabcsess like foci. Histocytes may demonstrate vacuolar cytoplasm and cellular phagocytosis (erythrophagocytosis and leukophagocytosis). Emperipolesis- Phagocytosis of RBCs, plasma cells/neutrophils is hallmark of disease. 44

45. Rosai – Dorfman disease . High-power view showing lymphocytophagocytosis by the sinus histiocytes. 45

46. Gout and Pseudogout Clinical features Males more commonly affected Onset in women occurs at very late age Risk factors- Age > 30 years, familial history of gout, alcohol use, obesity, thiazide administration, lead Gross description- Chalky white appearance of gouty deposit 46

47. Microscopy- early: edematous synovium with acute and chronic inflammatory infiltrate late: tophi These crystals are long, slender, needle shaped but difficult to visualize with routine staining Gouty deposits may be surrounded by fibrous tissue and be rimmed by histiocytes and giant cells 47

48. Cherub i s m Also known as ‘familial fibrous dysplasia of the jaws’, ‘disseminated juvenile fibrous dysplasia’, ‘familial multilocular cystic disease of the jaws’ and ‘Hereditary fibrous dysplasia of the jaws’ T he term Cherubism(reflecting the characteristic of chubby facial appearance similar) Point mutations in SH3BP2 gene on chromosome 4p16 Clinical Features: Affects in early childhood - mainly 1-5 yrs. P a i n l e s s b il a t eral f i rm s we ll i n g i n vo l v i n g t h e posterior mandible usually. 48

49. Radiographic features Bilateral multilocular lesions of the mandible more often than lesions of the maxilla. Cortices are frequently paper thin focally, Complete erosion and concomitant soft, tissue extension. Involvement of the coronoid process is common Condylar involvement is rare. 49

50. • Microscpy Vascular fibrous stroma is loosely arranged. MGC are small, few and usually aggregated focally. Peculiar perivascular eosinophilic cuffing. 50

51. Solitary bone cyst It is a fluid filled cyst of unknown etiology. Commonly in males under the age of 20. Usually occurs in long bones. Sites- Proximal humerus, proximal femur, pelvis and calcaneus (short bone) . 51

52. Typical solitary bone cyst of upper end of humerus abutting against epiphyseal plate complicated by fracture. (Soap bubble appearance). 52

53. Gross- Most are centered in metaphysis and they migrate away from epiphysis. Well delineated cyst filled with straw colored or blood stained serous fluid and is lined by smooth brown fibrous membrane. Cortex in thinned out. Periosteal bone proliferation in areas of fracture only. 53

54. Gross appearances of solitary bone cyst. A triangular lesion located in the upper end of the tibia. There has been secondary hemorrhage, leading to an appearance not too dissimilar to that of an aneurysmal bone cyst. Gross appearances of solitary bone cyst. A large lesion located in the upper metaphysis of the humerus. 54

55. Microscopy- Cyst wall lacks true cell lining. And consists of thin layer of fibrous tissue, composed of scattered fibroblasts, collagen fibers, fibrin deposits, which can undergo mineralization and resemble cementum. In case of previous pathologic fracture- Cyst wall may be thickened and may contain reactive fibroblasts, osteoclast type giant cells, haemosiderin deposits and reactive woven bone. 55

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57. Aneurysmal bone cyst Seen in patients between 10-20 years of age. Slightly common in females. It is a cystic lesion of bone most common in the vertebrae, flat bones and shaft of long bones. ABC may arise denovo - Primary ABC. Or areas resembling ABC can be found in other benign and malignant bone tumors - Secondary ABC such as in association with GCT of bone. Chondroblastoma. Osteoblastoma. Fibrous dysplasia and osteosarcoma. 57

58. X-ray- Lytic, involves metaphysis of long bones, is eccentric and shows blow-out appearance with extension into soft tissues. Periosteal new bone formation. 58

59. Radiographic appearance of aneurysmal bone cyst of lower end of fibula. Aneurysmal bone cyst of ulna 59

60. 60 Multiple blood filled cystic spaces separated by thin tan white septa

61. Microscopy- Large spaces: filled with blood no endothelial lining delimited by cells: fibroblasts, myofibroblasts and histiocytes. these cells also occupy septa that separate the cysts. row of osteoclasts often immediately beneath surface. D egenerated calcifying fibromyxoid tissue Septa also contains blood vessels, foci of oste oi d and bone. 61

62. Aneurysmal bone cyst of lower end of ulna. It is showing two cavities lined by osteoclast-like multinucleated giant cells. The intervening stroma is cellular but contains no neoplastic osteoid. 62

63. Aneurysmal bone cyst with multiple large giant cells and reactive bone at the periphery. 63

64. Clinical Features Age: in young persons, 20-30 years. Sex: Males>Females. P ain and swelling. Most common site → vertebral column. Mandible > Maxilla Occurs in Periosteal, cortical, or medullary location Benign Osteoblastoma (Giant osteoid osteoma) 64

65. Gross- Well delimited within either the cortex or cancellous bone. Hemorrhagic Gritty or granular consistency with cystic regions. 65

66. Microscopy- M any dila t ed ca pil lar ie s scattered throughout the tissue M ultinucleated giant cells scattered throughout the tissue The activ e ly p r o l i f er at i ng ost e oblas t s wh ich pa v e t h e irregular trabeculae of new bone It may or may not have a central sclerotic nidus The osteoblasts usually lack any significant atypia, having round to oval regular nuclei, often with prominent nucleoli. Mitotic activity is infrequent. 66

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69. Aggressive Osteoblastoma It is primarily defined by epithelioid osteoblasts, cells with abundant eosinophilic cytoplasm twice the size of conventional osteoblasts. These cells are frequently arranged in sheets with little or no intervening osteoid Cytologically, the neoplastic osteoblasts have abundant basophilic, finely granular cytoplasm with a perinuclear holo of less dense cytoplasm and an eccentric vesicular nucleus with a solitary prominent nucleolus 69

70. Chondroblastoma Rare (< 1% of primary bone neoplasms), Usually teenage males with open growth plate Painful lesion Sites: distal femur, proximal humerus , proximal tibia, pelvis, ribs, feet, scapula. Epiphysial, it may extend into the metaphyseal area or the articular cavity. Occasionally, it is found entirely in a metaphyseal location or in a small bone. Course: usually benign 70

71. Radiology- Extremely well circumscribed tumor of epiphysis with spotty calcifications in patient with open epiphysis 71

72. Gross - Well circumscribed, white - blue - gray , firm Usually 3 - 6 cm Variable calcification, necrosis, cystic areas 72

73. Microscopy- Polyhedral chondroblasts with hyperlobulated nuclei with grooves Chicken wire matrix Chondroid differentiation almost always present May have marked cellularity, intracytoplasmic glycogen granules, mitotic figures, necrosis, osteoclast - type giant cells No significant nuclear atypia 73

74. Chondromyxoid Fibroma Extremely rare benign bone tumor arising in young adults Age 15 - 25 years, no gender preference Presents with dull, achy pain Site: metaphysis of long tubular bones, small bones of feet or any bone, skull base. 74

75. Radiology - Extremely well circumscribed, lytic defect with scalloped, sclerotic margin similar to metaphyseal fibrous defect 75

76. Gross- 3 - 8 cm, well circumscribed, solid, glistening, yellow-white-tan, "old" tumor more hyalinized Replaces bone, and thins the cortex Resembles hyaline cartilage No myxoid change 76

77. Microscopy - Well circumscribed, hypocellular containing spindle cells and osteoclasts Tumor cells present in lacunae in myxoid areas, Atypia is common, including large, hyperchromatic nuclei Scattered calcification Extensive vascularity is present in peripheral areas No / rare mitotic activity 77

78. Giant Cell Tumor GCT is a true neoplastic process originating from the undifferentiated mesenchymal cells of the bone marrow Relatively uncommon tumor in jaw .Common in long bone like femur, tibia. Giant cell tumor usually occurs de novo but also may occur as a rare complication of Paget disease of the bone. GCTs arising in the head and neck region constitute approximately 2% of all GCTs. 78

79. It is more common in 3rd and 4th decades and unusual in patient below 20 years of age common in males Usually occurs at the end of long bones Pain and swelling at the affected site 79

80. 80 Radiology: Circumscribed lytic lesion surrounded by little or no sclerosis. The tumors may infrequently break through the cortex and invade the soft tissue or the articular space .

81. Microscopy: GCTs are composed of multinucleated giant cells in a vascular stroma of epitheloid or spindle-shaped mononuclear cells . Evenly distributed multinucleated giant cell with surrounding stroma made up of spindle cells are shown, which were consistent with GCT. 81

82. Giant cell tumor of tendon sheath Common, usually ages 30 - 50 years 2/3 female Primarily affects the fingers. Gross- Localized tumors up to 3cm in small joints (larger elsewhere), circumscribed, lobulated, white- gray -brown (yellow-orange-red color due to xanthoma cells and hemosiderin). 82

83. Microscopy Well circumscribed, lobulated, fairly well defined capsule Variable proportions of mononuclear cells (polyhedral cells with pale cytoplasm and round or grooved nuclei), osteoclast-like giant cells with 3 - 50 nuclei, fibroblastic elements, histiocytes and lymphocytes. May show mitotic figures Stroma is hyalinized Cartilaginous metaplasia rarely seen 83

84. OSTEOSARCOMA / OSTEOGENIC SARCOMA Sex- M>F Age – 3 rd and 4 th decade Site - metaphysial growth plates of extremities of long bones femur>tibia>humerus>skull or jaw>pelvis Mandible : Maxilla = 1.5:1 84

85. Classification of osteosarcoma Primary osteosarcomas Conventional-sub-typed as: Osteoblastic (50%) Chondroblastic (25%) Fibroblastic (25%) Small cell Telangiectatic Intraosseous well differentiated and Intracortical Surface osteosarcomas:-Parosteal, Periosteal, High grade surface 85

86. Secondary osteosarcomas Paget’s disease and after radiation exposure. Unusual forms of osteosarcoma subtypes of conventional osteosarcoma because their biological behavior is similar. Osteoblastic osteosarcoma-sclerosing type Osteosarcoma resembling osteoblastoma Chondromyxoid fibroma-like osteosarcoma Chondroblastoma-like osteosarcoma Clear-cell osteosarcoma Malignant fibrous histiocytoma-like osteosarcoma Giant cell rich osteosarcoma 86

87. Sunray or sunburst pattern Codmans triangle 87

88. Gross - Osteoblastic - white-tan, yellow in color, firm in consistency Chondroblastic - translucent lobules Fibroblastic - tan colored with soft or firm in consistency 88

89. Histological features Presence of osteoid formation by malignant osteoblasts Stro m al cel ls a re s p i n dle s h aped and a ty pi c a l w i th irregularly shaped nuclei The a m ount of m at r ix m at e ri a l prod u ced i n t h e tu m or varies considerably. Mitotic activity with frequent abnormal forms 89

90. Benign giant cells resembling osteoclasts are seen in about 25% of osteosarcomas . 90

91. CHONDROSARCOMA C h ondrosarco m a is a m al i gna n t t u m or chara c t eri z ed b y t h e formation of cartilage. Comprise about 10% of all primary tumors 1 % to 3% arise in the head and neck area. Types: Primary: arise directly from the cartilage Secondary: develop in a pre-existing benign cartilaginous tumor. 91

92. Clinical features Age: 6 th - 7 th decade No significant sex predilection Site: In head and neck → maxilla, mandible, base of the skull, cervical vertebrae, nasal cavity and nasal septum. P ainless mass or swelling, loosening of teeth. Maxillary tumors may cause nasal obstruction, congestion , epistaxis, photophobia, or visual loss. 92

93. Gross - On sectioning → lobular, blue-gray to gray-white, translucent, glistening surface, although firm, they are usually easily cut with a scalpel, except for areas with dense calcification or ossification. Necrosis within the center of the lobules is common. 93

94. Microscopy- Chondrosarcomas are composed of cartilage showing varying degrees of maturation and cellularitywith typical lacunar formation. Lobular growth pattern, with tumor lobules separated by thin fibrous connective tissue septa. Central areas of the lobules →greatest degree of maturation. Peripheral areas → immature cartilage & round or spindle shaped cells. Neoplastic cartilage may be replaced by bone in a manner similar to normal endochondral ossification. 94

95. Low-grade chondrosarcoma. The tumor cells are l a r ger t h an nor m al chon d ro c y te s , with larger, open-faced nuclei that have a uniform, fine chromatin pattern. Several mitotic figures are present, an uncommon finding in most chondrosarcomas High-grade chondrosarcoma. Hypercellular tumor contains pleomorphic cells, some with large, bizarre nuclei. A few cells are spindle shaped 95

96. Variants Clear cell chondrosarcoma Myxoid chondrosarcoma Mesenchymal chondrosarcoma Dedifferentiated chondrosarcoma 96

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98. Metastases Metastatic bone tumors are the most common malignan t tumors of the skeleton. Approximately 70% of all malignant tumors are metastatic in origin. Metastases are usually found in: Vertebrae – especially posterior vertebral body, extending into pedicle, pelvis, proximal femur, proximal humerus and skull. Types : osteolytic metastases sclerotic/osteoblastic metastases mixed lytic and sclerotic metastases 98

99. Bone involvement in metastases occurs by means of 3 main mechanisms: (1) direct extension (2) retrograde venous flow (3) seeding with tumor emboli via the blood circulation which is the most common route of spread. 99

100. Usually no periosteal reaction May appear as moth-eaten, permeative or geographic lesions Indistinct zones of transition, no sclerotic margins and may be sharply circumscribed or have indistinct borders Lesions distal to elbows and knees - 50% are from lung and breast Diffuse skeletal sclerosis or multiple round, well-circumscribed sclerotic lesions - Prostate & Breast Expansile and lytic (soap-bubbly) – RCC Cookie-bite lesions of the cortices of long bones – Lung 100

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103. Approach to giant cell lesions 103

104. SUMMARY 104

105. References Fletcher D. M. C. Diagnostic Histopathology of Tumors. In: Tumors of the osteoarticular system, 4ed. Elsevier;2013.p1541-606. Rosai J. Rosai and Ackerman’s Surgical Pathology. In: Bone and joint, 10ed. Elsevier;2011.p2012-103. Weidner,Cote , Suster,Weiss . Modern Surgical Pathology. In: Oral Cavity and Jaws, 2ed. Elsevier;2009.p343-356. Carrie Y. Inwards K. Krishnan Unn . V. Sternberg’s Diagnostic Surgical Pathology. In: Bone Tumors, 6ed.Wolters Kluwer;2015.p254-97. 105

106. Thank you 106

107. Post test- 2marks-2mins What is the diagnosis for the following cases ? 107

108. Case 1 32 year old man 108

109. Case 2 18 year old man with 2 year history of mild knee pain 109

110. Case 3 A 65-year-old Caucasian male 110

111. Case 4 111 A 56 year old woman presented with history of left cheek swelling for last 5 years CT scan (Coronal) showing expansile and destructive lesion involving left maxilla

112. Intra operative picture showing extensive tumor being excised 112

113. Case 5 15 year old girl 113

114. Answers 1- Central giant cell granuloma 2- Synovial giant cell tumor 3- Clear-cell chondrosarcoma 4- Giant Cell Rich Osteosarcoma 5- Chondromyxoid fibroma 114